There was no significant difference seen in overall survival between the two arms.

The adverse event rates were generally similar between both arms.

There were more thromboembolic events, endometrial cancers and endometrial biopsies seen with tamoxifen.

There were more cardiac events, joint problems and diagnoses of hypercholesterolemia in the letrozole arm.

Author's Conclusions

Five years of letrozole improves disease free survival compared to five years of tamoxifen when given as adjuvant therapy in hormonally responsive breast cancers.

In particular, letrozole seems to improve rates of distant metastasis compared with tamoxifen.

The two medications have similar low rates of adverse events, although the types of events differ.

Further follow-up is needed to solidify the superiority of letrozole over tamoxifen, and future analyses will examine the crossover patients.

Clinical/Scientific Implications

This abstract reports data from a large, well designed randomized phase III double blind trial comparing letrozole to tamoxifen. The major criticism of this abstract is that the median follow-up time for these patients was short. Twenty-six months is considered a short follow-up time in breast cancer given the known natural history of this disease. However, if this trial is compared to another similarly designed trial of aromatase inhibitors versus tamoxifen ( the ATAC trial anastrazole for 5 years vs. tamoxifen for 5 years), one notices very similar survival curves. The magnitude of the improvement in disease free survival calculated in this trial of 2.6% is remarkably similar to the benefit seen in the ATAC trial, and the ATAC trial had 5 years of median follow-up. It seems reasonable to predict that this trial will demonstrate similar results at 5 years. Although the rate of adverse events in this trial was low, physicians who use this medication must counsel their patients about the specific risks of letrozole compared to tamoxifen, including risks of cardiac events and hypercholesterolemia. Finally, society as a whole needs to consider the magnitude of the benefit of this medication compared to tamoxifen while remembering its significantly higher price tag.

May 29, 2014 - The American Society of Clinical Oncology is updating its guidelines on adjuvant endocrine therapy to recommend tamoxifen for up to 10 years for women with nonmetastatic hormone receptor-positive breast cancer. This updated clinical practice guideline was published online May 26 in the Journal of Clinical Oncology.